The role of the hexokinase isoenzymes in the regulation of adipose tissue glucose utilization and insulin sensitivity will be assessed, with particular attention to abnormalities in diabetes mellitus and endogenous hypertriglyceridemia. The project is divided into 5 sections: I. Mechanisms of control of hexokinase isoenzymes by substrates and hormones during in vitro incubations of rat and human adipose tissue; II. Control of adipose tissue hexokinase enzymes in rats by dietary composition and quantity; III. Effect of dietary carbohydrate content on hexokinase isoenzymes, glucose utilization and lipolysis in adipocytes from normal and hypertriglyceridemic patients on controlled diet; IV. Effect of treatment of diabetes mellitus and insulin resistant states in man on adipose tissue hexokinase isoenzymes and glucose utilization; and V. Effect of hypolipideic drugs and other agents active on adipose tissue, in vitro and in vivo, on human adipose tissue lipogenesis and lipolysis. In all sections we will study the relationship between the enzyme activities and insulin sensitivity. In addition, in sections III-V we will try to correlate in vitro with in vivo metabolism. The ultimate goal is to improve our understanding of the control mechanisms of adipose tissue and the ways to manipulate them therapeutically in human disease.